Bacterial load and related innate immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease

Abstract

Background: Characterization of COPD patients with rapid lung functional decline is of interest for prognostic and therapeutic reasons. We recently reported an impaired humoral immune response in rapid decliners.

Objective: To determine the microbiota associated to markers of innate immune host response in COPD patients with rapid lung functional decline.

Methods: In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the microbiota and related markers of immune response was measured in bronchial biopsies of patients with different lung functional decline (rate of FEV1% lung functional decline: no decline FEV1%, ≤20 ml/year n = 21, slow decline FEV1%, >20 ≤ 70 ml/year, n = 14 and rapid decline FEV1%, >70 ml/year, n = 15) using qPCR for microbiota and immunohistochemistry for cell-receptors and inflammatory markers.

Main results: Pseudomonas aeruginosa and Streptococcus pneumoniae were increased in rapid decliners vs slow decliners, S. pneumoniae was also increased compared to non decliners. In all patients, S. pneumoniae (copies/ml) positively correlated with pack-years consumption, lung function decline, TLR4, NOD1, NOD2 scored in bronchial epithelium and NOD1/mm² in lamina propria.

Conclusion: These data show an imbalance of microbiota components in rapid decliners which is associated to the expression of the related cell-receptors in all COPD patients. These findings may help in the prognostic stratification and treatment of patients.

Keywords: Airway inflammation; COPD; Chronic diseases; Microbiota; Outcome; Prevention; Rehabilitation; Viruses.